Abstract：
:Advanced-stage epithelial ovarian cancers are amongst the most difficult to treat tumors and have proven to be refractory to most cytotoxic, molecularly targeted, or immunotherapeutic approaches. Here, we report that nanoparticle-drug conjugates (NDCs) of monomethyl auristatin E (MMAE) significantly increase loading on a per-vehicle basis as compared to antibody-drug conjugates (ADCs). Their intraperitoneal administration enabled triggered release of the active MMAE toxin to inhibit tumor growth and to extend animal survival to >90 days in a cell-line xenograft model of disseminated ovarian cancer. In a patient-derived xenograft model of advanced-stage and platinum-resistant ovarian cancer, an MMAE-based NDC doubled the duration of tumor growth inhibition as compared to cisplatin. NDCs of highly potent toxins thus introduce a translatable platform that may be exploited to maximize the safety and efficacy of cytotoxic chemotherapies, combining the best features of ADCs with those of nanoparticle-based therapeutics.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Qi R,Wang Y,Bruno PM,Xiao H,Yu Y,Li T,Lauffer S,Wei W,Chen Q,Kang X,Song H,Yang X,Huang X,Detappe A,Matulonis U,Pepin D,Hemann MT,Birrer MJ,Ghoroghchian PPdoi
10.1038/s41467-017-02390-7subject
Has Abstractpub_date
2017-12-18 00:00:00pages
2166issue
1issn
2041-1723pii
10.1038/s41467-017-02390-7journal_volume
8pub_type
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